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Test ID: 3A5Q Cytochrome P450 3A5 Genotype, Varies


Ordering Guidance


Testing is available as the single gene assay (this test) and as a part of a psychotropic or focused pharmacogenomics panel.

 

If multiple pharmacogenomic genotype testing is desired, order PGXQP / Focused Pharmacogenomics Panel, Varies.

 

If genotype testing for psychotropic medications is desired, order PSYQP / Psychotropic Pharmacogenomics Gene Panel, Varies.



Additional Testing Requirements


In general, most drugs metabolized by CYP3A5 are also metabolized by CYP3A4 and usually to a greater degree than CYP3A5. For this reason, substrates of these 2 enzymes are sometimes listed together in publications and genotyping of both genes might be needed to fully understand the metabolism of these drugs and predict phenotype. If CYP3A4 genotyping is needed, order 3A4Q / Cytochrome P450 3A4 Genotype, Varies.



Specimen Required


Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List in Special Instructions for a list of tests that can be ordered together.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: One swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient

 

Specimen Type: DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.

2. Include concentration and volume on tube.


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-Therapeutics Test Request (T831)

Useful For

Aids in optimizing treatment with tacrolimus and other drugs metabolized by cytochrome P450 3A5

Method Name

Polymerase Chain Reaction (PCR) With Allelic Discrimination Analysis

Reporting Name

CYP3A5 Genotype, V

Specimen Type

Varies

Specimen Minimum Volume

Blood: 0.4 mL
Saliva: 1 swab

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

CYP3A5 is a member of the CYP3A family of genes located on chromosome 7. The cytochrome P450 (CYP) 3A subfamily of enzymes responsible for the metabolism of more than 50% of medications that undergo hepatic metabolism and first-pass metabolism in intestinal epithelial cells. The CYP3A5 expression level and enzymatic activity can be modulated by genetic variation. CYP3A5 allelic frequency depends upon ethnicity. For example, in individuals of European descent the most common allele is the CYP3A5*3 allele (c.219-237A>G), which results in a splicing defect and absence of enzyme activity. In individuals of African descent, the *1 allele (functional enzyme) is most common. The distribution of CYP3A5*3 allele frequencies ranges from 0.14 among sub-Saharan Africans to 0.95 in European populations.

 

CYP3A5 testing is commonly ordered for patients receiving tacrolimus. Tacrolimus is an immunosuppressive calcineurin inhibitor used in transplant recipients. Tacrolimus has a low therapeutic index with a wide range of side effects and large interindividual variability in its pharmacokinetics, particularly in the dose required to reach target trough blood concentrations, thus necessitating routine therapeutic drug monitoring in clinical practice.

 

Tacrolimus dose requirements are most closely associated with CYP3A5 genotype even though the drug is metabolized by both CYP3A4 and CYP3A5. According to existing literature and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, individuals with at least one copy of fully functional CYP3A5 (ie, *1/*1 and *1/*3) require a higher dose of tacrolimus to reach the targeted whole blood concentrations than those without a copy of a fully functional CYP3A5 allele (ie, *3/*3) (2-5). CYP3A5 genotyping may predict dose requirements for tacrolimus but does not replace the need for therapeutic monitoring to guide tacrolimus dose adjustments. For a patient with the CYP3A5*3/*3 genotype, initiating tacrolimus therapy with a standard (normal) dose is recommended. One of the complications in interpreting CYP3A5 genotyping results and the effect of genotype on drug dosing is the fact that most individuals involved in drug trials have been of European decent. Individuals of European decent are more likely to have the CYP3A5*3/*3 genotype, which predicts a poor metabolizer phenotype. Dosing requirements were derived from these clinical trials so individuals with 1 or 2 copies of CYP3A5*1, will functionally behave as though they have increased activity and may require higher doses of CYP3A5 metabolized drugs.

 

The following table displays the CYP3A5 variants detected by this assay, the corresponding star allele, and the effect on CYP3A5 enzyme activity:

CYP3A5 allele

cDNA nucleotide change

(NM_000777.4)

Effect on enzyme activity

*1

None (wild type)

Normal activity

*3

c.219-237A>G

No activity

*5

c.432+2T>C

No activity

*6

c.624G>A

No activity

*7

c.1035dup

No activity

*8

c.82C>T

Reduced activity

*9

c.1009G>A

Reduced activity

Reference Values

An interpretive report will be provided.

Interpretation

An interpretive report will be provided.

 

The genotype, with associated star alleles, is assigned using standard allelic nomenclature as published by Pharmacogene Variation (PharmVar) Consortium.(1)

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Clinical Reference

1. PharmVar: Pharmacogene Variation Consortium. Updated March 3, 2021. Accessed March 22, 2021. Available at www.pharmvar.org/

2. Birdwell KA, Decker B, Barbarino JM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015;98(1):19-24. doi: 10.1002/cpt.113

3. Thervet E, Loriot MA, Barbier S, et al. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther. 2010;87(6):721-726. doi: 10.1038/clpt.2010.17

4. Lamba J, Hebert JM, Schuetz EG, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenet Genomics. 2012;22(7):555-558. doi: 10.1097/FPC.0b013e328351d47f

5. Clinical Pharmacogenetics Implementation Consortium (CPIC). Accessed October 14, 2020. https://cpicpgx.org/

Day(s) Performed

Monday through Friday

Report Available

3 to 8 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81231-CYP3A5

LOINC Code Information

Test ID Test Order Name Order LOINC Value
3A5Q CYP3A5 Genotype, V 81140-6

 

Result ID Test Result Name Result LOINC Value
610117 CYP3A5 Genotype 81140-6
610118 CYP3A5 Phenotype 79717-5
610119 Interpretation 69047-9
610120 Additional Information 48767-8
610121 Method 85069-3
610122 Disclaimer 62364-5
610123 Reviewed by 18771-6
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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